Patients with SLE have excessive B cell proliferation. They have increased proliferation of bone marrow stem cells and circulating B cell precursors. Disease activity is characterized by a switch from just proliferation to differentiation and immunoglobulin synthesis. In some patients the T cell regulation of B cell functions is abnormal. In an attempt to better understand cell-cell interactions, normals were studied for the capacity of T cells to respond to autologous non-T cells. IL 2 production by T4+ cells was necessary for the proliferation of T8+ (suppressor) cells. This function is subnormal in patients with SLE. Monoclonal antibodies were used to study subpopulations of SLE patients. One subset, with a reduced ratio of helper/suppressor cells, was characterized clinically by renal disease, thrombocytopenia, leukopenia and early age of onset of disease. Another subset had a high ratio and a clinical picture which included muscle and lung disease, Sicca syndrome, lympadenopathy and CNS disease. Thus, SLE may not be a single disease, but a group of syndromes with different genetic and cellular bases. SLE patients have a variety of T cell defects. These are largely explained by anti-T cell antibodies produced by the B cells of these patients. The more rapidly progressive autoimmune lymphoproliferative disorder, angioimmunoblastic lymphadenopathy is characterized by markedly effective helper T cells which drive B cells to proliferate and differentiate. The B cells themselves are normal in this variant. Proto-oncogene expression is abnormal in patients with SLE. There is a significant increase in c-myc expression.